A case-control study has found that a simple test can indicate the presence of non-alcoholic steatosis by measuring caspase 3-generated cytokeratin-18 fragments in the blood. The test could eliminate the need for invasive liver biopsies, currently the only reliable way to diagnose the disease.
The results of the study are published in the July 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both children and adults. While simple steatosis – an accumulation of fat in the liver – is the usual form and is benign, nonalcoholic steatohepatitis (NASH) can be a very serious condition. As many as 25 percent of patients progress to cirrhosis and can have complications like liver failure and hepatocellular carcinoma. But until now, only an invasive liver biopsy, which carries a risk of complications, could distinguish between the two.
Led by Anna Wieckowska, M.D. of the Department of Gastroenterology and Hepatology at the Cleveland Clinic Foundation, researchers considered a non-invasive way to diagnose NASH and assess histologic severity using a simple blood test. They looked for indicators of liver cell death, specifically, caspase-generated CK-18 fragments which have been shown to label early apoptotic cells.
They tested the blood of 39 patients undergoing liver biopsy for suspected NAFLD and compared the results to the biopsies, and also to the blood of 35 healthy age-matched controls.
The plasma levels of CK-18 fragments ranged from 105.5 to 2306.4 U/L and were significantly higher in patients undergoing liver biopsy compared to the healthy controls. The levels were strikingly higher in patients whose liver biopsies resulted in a definite diagnosis of NASH, compared with patients whose liver biopsies showed no NASH, or were normal.
Additionally, caspase activity levels independently predicted the presence of NASH. The risk of definitive NASH on liver biopsy increased with increasing plasma levels of caspase 3-generated CK-18 fragments. For every 50 U/L increase in CK-18 levels, the likelihood of having "definitive NASH" increased 86 percent.
"In summary, our findings suggest that non-invasive monitoring of hepatocyte apoptosis in blood of patients with NAFLD is a reliable tool to differentiate NASH from 'not NASH' in patients with suspected NAFLD," the authors report.
The test showed high sensitivity, specificity, and positive and negative predictive value, leading the authors to suggest it as an important potential clinical tool. "Future large studies are needed to confirm these observations," they conclude. And they are currently planning a large multi-center prospective validation study.
Article: "In Vivo Assessment of Liver Cell Apoptosis as a Novel Biomarker of Disease Severity in Nonalcoholic Fatty Liver Disease," Anna Wieckowska, Nizar N. Zein, Lisa M. Yerian, A. Rocio Lopez, Arthur J. McCullough, Ariel E. Feldstein, Hepatology; July 2006 (DOI: 10.1002/hep.21223).
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